Regular exercise suppresses steatosis-associated liver cancer development by degrading E2F1 and c-Myc via circadian gene upregulation.

Regular exercise is believed to suppress cancer progression. However, the precise molecular mechanisms by which exercise prevents cancer development remain unclear. In this study, using a steatosis-associated liver cancer mouse model, we found that regular exercise at a speed of 18 m/min for 20 min daily suppressed liver cancer development. To explore the underlying mechanisms, we examined the gene expression profiles in the livers of the exercise and non-exercise groups. The expressions of circadian genes, such as Per1 and Cry2, were upregulated in the exercise group. As circadian rhythm disruption is known to cause various diseases, including cancer, improving circadian rhythm through exercise could contribute to cancer prevention. We further found that the expression of a series of E2F1 and c-Myc target genes that directly affect the proliferation of cancer cells was downregulated in the exercise group. However, the expression of E2F1 and c-Myc was transcriptionally unchanged but degraded at the post-translational level by exercise. Cry2, which is regulated by the Skp1-Cul1-FBXL3 (SCFFBXL3) ubiquitin ligase complex by binding to FBXL3, can form a complex with E2F1 and c-Myc, which we think is the mechanism to degrade them. Our study revealed a previously unknown mechanism by which exercise prevents cancer development.

Social contact impacts physical activity and sedentary behavior among older adults in Japan due to COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has adversely affected social contact and physical activity. This study investigated the correlation between physical activity, social contact, and sedentary time among adults aged 65 years and above during the COVID-19 pandemic. METHODS: This study was conducted in N City, H Prefecture, Japan. The authors randomly selected 4,996 adults, aged 65 years and above (mean age 74.1 ± 6.1 years), living in N City, and survey forms were distributed by mail in mid-August 2020. Altogether, 1,925 participants were included in this study. The survey comprised questions concerning the participants' sex, height, weight, age, smoking and drinking habits, living arrangements, social contact assessments, physical activity levels, and sedentary time. Moreover, linear regression analysis was utilized to investigate the associations between the variables. RESULTS: The reported median physical activity was 1272 metabolic equivalent of task-min/week (interquartile range 528-2628), and the reported median sedentary time was 360 min/week (interquartile range 240-600). COVID-19 "somewhat," "quite a lot," or "completely" hindered the frequency of in-person contact with friends among 75.5% of the respondents and hampered the frequency of virtual contact with friends among 38.8% of the respondents. Physical activity was associated significantly with in-person contact indicators: "interaction with friends" (B = -0.111; 95%CI: -0.187, -0.035; p = 0.004) and "social participation" (B = -0.163; 95%CI: -0.248, -0.079; p < 0.001). These associations remained significant for both multivariate analysis Models 1 (sex and age) and 2 (addition of body mass index [BMI], alcohol use, smoking, living alone, and the number of illnesses to Model 1). Additionally, sedentary time was significantly associated with the social contact variable of "interaction with friends" (B = 0.04; 95%CI: 0.016, 0.064; p = 0.001). This association remained significant in both multivariate analysis models. CONCLUSIONS: Significant associations were confirmed between reduced social contact, decreased physical activity, and more sedentary behavior among older adults due to COVID-19. Hence, continuous monitoring and support for social activities among susceptible older adults in extraordinary circumstances are essential.

Lower dietary variety is associated with worse sleep quality in community-dwelling elderly Japanese women.

BACKGROUND AND OBJECTIVES: Sleep disturbance is a common health problem in the elderly population. We examined the association between dietary variety and subjective sleep quality in community-dwelling elderly Japanese women. METHODS AND STUDY DESIGN: This cross-sectional study recruited 160 community-dwelling elderly women aged ≥65 years. Subjective sleep quality and dietary variety were assessed by Pittsburgh Sleep Quality Index (PSQI) and dietary variety score (DVS), respectively. DVS was calculated from the eating frequency of 10 food groups. Sleep disturbance was defined as PSQI score of ≥6. RESULTS: The DVS in subjects with sleep disturbance was significantly lower than that of those without the disturbance (4.1±2.1 vs 5.3±2.1, p<0.01). In the multivariable regression model, the PSQI score was negatively correlated with the DVS score in age-adjusted model (standardized coefficient; -0.234, p<0.01). In the further adjusted model that included depression levels, the negative association between PSQI score and DVS score was retained (standardized coefficient; -0.211, p<0.05). Among 10 food groups comprising DVS, the eating frequency of soybean and soybean products was the determinant of sleep disturbance in the stepwise liner regression analysis. In the further model that contained DVS, DVS was the independent determinant of sleep disturbance, while the eating frequency of soybean and soybean products was excluded. CONCLUSIONS: A worse sleep quality was associated with lower DVS in elderly Japanese women. Diet comprising various food groups was better for sleep quality than consuming only a particular food in the elderly.

Low Dietary Variety Is Associated with Incident Frailty in Older Adults during the Coronavirus Disease 2019 Pandemic: A Prospective Cohort Study in Japan.

BACKGROUND: Stagnation of social activity due to the COVID-19 pandemic probably reduces motivation to maintain a healthy diet. It is important to report on the dietary changes observed in older adults during a period of restriction on outings and to clarify the relationship between dietary variety and frailty. This one-year follow-up study examined the association between frailty and dietary variety during the COVID-19 pandemic. METHODS: Baseline and follow-up surveys were conducted in August 2020 and August 2021, respectively. The follow-up survey was distributed by mail to 1635 community-dwelling older adults aged ≥65 years. Of the 1235 respondents, 1008 respondents who were non-frail at baseline are included in this study. Dietary variety was examined using a dietary variety score developed for older adults. Frailty was assessed using a five-item frailty screening tool. The outcome was frailty incidence. RESULTS: In our sample, 108 subjects developed frailty. A linear regression analysis revealed a significant association between dietary variety score and frailty score (ß, -0.032; 95% CI, -0.064 to -0.001; p = 0.046). This association was also significant in Model 1, adjusted for sex and age, (ß, -0.051; 95% CI, -0.083 to -0.019; p = 0.002) and in a multivariate analysis that added adjustments for living alone, smoking, alcohol use, BMI, and existing conditions to Model 1 (ß, -0.045; 95% CI, -0.078 to -0.012; p = 0.015). CONCLUSIONS: A low dietary variety score was associated with an increased frailty score during the COVID-19 pandemic. The restricted daily routine caused by the COVID-19 pandemic will probably continue to have a long-term effect in terms of reduced dietary variety. Thus, vulnerable populations, such as older adults, might require dietary support.

Association between asymmetric dimethylarginine and sarcopenia in community-dwelling older women.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelium nitric oxide synthesis and causes endothelial dysfunction that may be related to sarcopenia. However, the association between ADMA and sarcopenia has not been studied. We evaluated the correlations between plasma ADMA levels and sarcopenia in community-dwelling older women. In total, 144 community-dwelling older women participated in this study. Plasma ADMA levels were measured using a competitive enzyme-linked immunosorbent assay. Skeletal muscle mass, measured in terms of bioimpedance and grip strength, was used to assess sarcopenia. Plasma ADMA levels were significantly higher in participants with sarcopenia than in those without sarcopenia. Through receiver-operating characteristic curve analysis, the cutoff value of plasma ADMA level for sarcopenia was estimated at 0.57 µM. Sarcopenia was significantly more prevalent in participants with higher plasma ADMA levels than in those with lower plasma ADMA levels. According to logistic regression analysis, the crude odds ratio of higher plasma ADMA levels in participants with sarcopenia was 4.57 (95% confidence interval, 1.82-11.47; p = 0.001). Reductions in the skeletal muscle mass index over 2 years were significantly greater in participants with higher plasma ADMA levels. In conclusion, plasma ADMA levels were significantly associated with sarcopenia in community-dwelling older women.

Oral Microbial Profile Analysis in Patients with Oral and Pharyngeal Cancer Reveals That Tumoral Fusobacterium nucleatum Promotes Oral Cancer Progression by Activating YAP.

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.

Effects of 4G-beta-D-Galactosylsucrose in patients with depression: A randomized, double-blinded, placebo-controlled, parallel-group comparative study.

Advances in genetic research on microbiome have led to several trials on the effectiveness of synbiotics or probiotics in patients with depression; however, none have evaluated the efficacy of prebiotics. 4G-beta-D-Galactosylsucrose (Lactosucrose, LS) is selectively assimilated by Bifidobacterium as a prebiotic and improves microbiome diversity. However, as it is not clear if LS consumption can improve symptoms of depression, we investigated whether LS intake can improve depressive symptoms, quality of life (QOL), and self-efficacy by conducting a single cite, double-blinded, randomized controlled trial in 20 outpatients with depressive episodes (F32, ICD-10) for 24 weeks. Participants (age range, 36-72 years) were randomized to the LS (n = 9) or placebo groups (n = 11). Primary outcome was improvement in total Montgomery Asberg Depression Rating Scale (MADRS) score, and the secondary outcomes were MADRS subscores, global self-efficacy scale (GSES) score, World Health Organization QOL (WHO/QOL-26) score, and 16S rRNA analysis of the fecal microbiome. LS consumption did not significantly improve total MADRS scores (-2 (-16 to 16) vs 0 (-6 to 10), p = 0.552), but GSES tended to improve in the LS group (2.00 ± 4.24 vs -1.36 ± 4.15, p = 0.091) with a large effect size (Cohen's d = 0.802). Sequencing of 16S rRNA revealed individual-level differences in microbiome diversity changes due to the intervention. Thus, we show that LS intake can improve self-efficacy, but not depressive symptoms, even in a small sample. Additional studies that also regulate diet and ensure adherence may help determine a correlation between depression and the gut microbiome.

Association of family history of type 2 diabetes with blood pressure and resting heart rate in young normal weight Japanese women.

OBJECTIVE: We suggested association of family history of type 2 diabetes (FHD) with microvascular dysfunction, which may cause blood pressure (BP) elevations. We test whether FHD may be associated with higher BP. RESEARCH DESIGN AND METHODS: Resting BP, heart rates (in beats per minute: bpm), body composition and fasting concentrations of glucose, insulin, leptin and adiponectin were measured in 332 Japanese women aged 18-24 years. They were grouped according to BP category defined by the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. RESULTS: BMI averaged < 22 kg/m2 and did not differ cross-sectionally between 73 with (FHD+) and 259 without FHD (FHD-). FHD+ had higher mean (81 ± 9 vs. 77 ± 7 mmHg, p < 0.001), systolic (111 ± 13 vs. 106 ± 10 mmHg, p = 0.003) and diastolic BP (65 ± 8 vs. 60 ± 7 mmHg, p < 0.001). Prevalence of elevated BP (11.0 vs. 6.2%), hypertension stage 1 (4.1 vs. 0.8%) and stage 2 (2.7 vs. 0.4%) was higher as well (p = 0.01). Endurance training in FHD+ abolished the differences in BP readings and BP prevalence. However, the mean resting heart rate in FHD+ athletes (61.2 bpm) was close to those in FHD+ (64.7 bpm) and FHD- nonathletes (64.6 bpm) and was higher than in FHD- athletes (56.5 bpm). Fat mass and distribution evaluated by dual-energy X-ray absorptiometry, markers of insulin resistance, and serum adipokines studied did not differ between the two groups. CONCLUSIONS: FHD was associated with higher BP and higher prevalence of elevated BP and hypertension, suggesting contribution of microvascular dysfunction in BP elevations in normal weight young Japanese women. FHD may be associated with reduced heart rate response to endurance training as well.

Birth weight was associated positively with gluteofemoral fat mass and inversely with 2-h postglucose insulin concentrations, a marker of insulin resistance, in young normal-weight Japanese women.

Introduction: We tested whether birth weight might be associated with gluteofemoral fat mass and insulin sensitivity later in life. Materials and methods: Body size trajectory since birth, body composition at age 20, and markers of insulin resistance were measured in 316 Japanese women. A subset of 148 women underwent a 75 g oral glucose tolerance test. Multiple linear regression analyses were used to identify most important determinants of birth weight. Results: Birth weight was correlated positively with height and weight at age 12, 15, and 20 years (all p < 0.001 except for weight at 12 years, p = 0.03). Although it showed no correlation with BMI at age 12 and 15, it was correlated positively with current BMI (p = 0.006). It showed positive correlations with lean mass in arms, legs, trunk, and the whole body at age 20 (all p < 0.001). Additionally, it was correlated positively with leg (gluteofemoral) fat mass (p = 0.007), although there was no correlation with total body and trunk fat mass. Furthermore, weight at birth showed inverse correlations with 2-h postglucose insulin concentrations (p = 0.008) whereas it was not correlated with fasting insulin and homeostasis model assessment-insulin resistance. In a multiple regression analysis, which included anthropometric and biochemical variables as independent variables, appendicular muscle mass (standardized ß 0.394, p < 0.001) emerged as a single determinant of birth weight (R 2 = 0.15). In a model which included gluteofemoral fat mass and 2-h postglucose insulin, birth weight was associated with gluteofemoral fat mass (standardized ß 0.240, p = 0.003) and 2-h postglucose insulin concentrations (standardized ß - 0.217, p = 0.007) (R 2 = 0.09). Conclusions: Birth weight was associated positively with gluteofemoral fat mass and inversely with 2-h postglucose insulin concentrations, a marker of insulin resistance.

Ubiquitin promoter-terminator cassette promotes genetically stable expression of the taste-modifying protein miraculin in transgenic lettuce.

Lettuce is a commercially important leafy vegetable that is cultivated worldwide, and it is also a target crop for plant factories. In this study, lettuce was selected as an alternative platform for recombinant miraculin production because of its fast growth, agronomic value, and wide availability. The taste-modifying protein miraculin is a glycoprotein extracted from the red berries of the West African native shrub Richadella dulcifica. Because of its limited natural availability, many attempts have been made to produce this protein in suitable alternative hosts. We produced transgenic lettuce with miraculin gene driven either by the ubiquitin promoter/terminator cassette from lettuce or a 35S promoter/nos terminator cassette. Miraculin gene expression and miraculin accumulation in both cassettes were compared by quantitative real-time PCR analysis, Western blotting, and enzyme-linked immunosorbent assay. The expression level of the miraculin gene and protein in transgenic lettuce was higher and more genetically stable in the ubiquitin promoter/terminator cassette than in the 35S promoter/nos terminator cassette. These results demonstrated that the ubiquitin promoter/terminator cassette is an efficient platform for the genetically stable expression of the miraculin protein in lettuce and hence this platform is of benefit for recombinant miraculin production on a commercial scale.

Relationship Between Dietary Variety and Frailty in Older Japanese Women During the Period of Restriction on Outings Due to COVID-19.

OBJECTIVES: To investigate the relationship between diet and frailty in community-dwelling older adults during the period of restriction on outings due to novel coronavirus disease 2019 (COVID-19). METHOD: A mail survey targeting adults aged 65 years or older, including questions on sex, age, height, weight, and social participation, was conducted in May 2020. The participants' dietary variety score and frailty score were then calculated. RESULTS: Overall, 322 women aged 65 years or older and who were living in the community were recruited for the study; 253 were finally analyzed. The mean age of the 253 participants was 80.0 ± 6.4 years. The dietary variety score and frailty scores were significantly correlated in the linear regression analysis (ß: -0.224, p < .001). In the multivariate regression analysis, these factors remained significantly correlated in Model 1, which was adjusted for age (ß: -0.229, p < .001), and Model 2, which was adjusted for age, body mass index, and other confounding factors (ß: -0.208, p = .001). DISCUSSION: Diet was correlated with frailty in older adults living in the community during the period of restriction on outings due to COVID-19.

Relationship Between Social Activity and Frailty in Japanese Older Women During Restriction on Outings due to COVID-19.

BACKGROUND: This study investigated the relationship between social activities and frailty during the restriction on outings due to COVID-19. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: This study was conducted in City Nishinomiya of Prefecture Hyogo, in Japan. A mail survey was carried out among women aged 65 years or older in May 2020. A population of 293 women aged 65 years or older living in the community was recruited for the study and 213 of them were analyzed. MEASUREMENTS: The survey included questions on sex, age, height, weight, and social activity. Social activity consisted of participation in social organizations and their frequency, as well as frequency of interaction with family and friends. The survey also asked if regular social activity had been impeded by COVID-19. RESULTS: A significant association was found between frailty and hindered interaction with friends (ß: 0.176, p = .014). Multivariate linear regression analysis confirmed that this association was also significant in Model 1 (ß: 0.158, p = .025), and Model 2 (ß: 0.148, p = .034). CONCLUSIONS: No association between being hindered in social activity and frailty was found in older women living in the community during the restriction on outings due to COVID-19.

Associations of serum transthyretin with triglyceride in non-obese elderly Japanese women independently of insulin resistance, HDL cholesterol, and adiponectin.

OBJECTIVE: Studies are limited on the association between serum transthyretin (TTR), a negative acute phase reactant, and triglyceride (TG). RESEARCH DESIGN AND METHODS: TG, TTR, and insulin resistance-related cardiometabolic variables were measured in 159 fasting and 185 nonfasting community-dwelling elderly women aged 50-96 years. Pearson correlation analysis and then stepwise multiple regression analyses were performed to further identify the most significant variables contributing to the variation of fasting and nonfasting TG. RESULTS: Multiple regression analysis for fasting TG as a dependent variable revealed that TTR (standardized ß: 0.299) and HDL cholesterol (standardized ß: -0.545) emerged as determinants of TG independently of percentage of body fat, homeostasis model assessment insulin resistance, serum leptin and adiponectin, and plasminogen activator inhibitor-1 (PAI-1) (R 2 = 0.36). For nonfasting TG, HDL cholesterol (standardized ß: - 0.461), TTR (standardized ß: 0.231), nonfasting insulin, a marker of insulin resistance, (standardized ß: 0.202), and PAI-1 (standardized ß: 0.187) emerged as determinants independently of percentage of body fat, nonfasting glucose, serum leptin and adiponectin, and high-sensitivity C-reactive protein (R 2 = 0.45). CONCLUSIONS: Fasting and nonfasting TG showed positive association with TTR in community-dwelling elderly non-obese women independently of insulin resistance, HDL cholesterol, and adiponectin. These findings may provide a clue as to a physiological function of circulating TTR in human: an influence factor of TG-rich lipoproteins in the circulation.

Higher circulating orosomucoid and lower early-phase insulin secretion in midlife Japanese with slower glucose disposal during oral glucose tolerance tests.

OBJECTIVE: We examined whether serum orosomucoid, an acute phase protein as with C-reactive protein, in addition to insulin resistance and beta-cell dysfunction, was involved in glucose disposal during oral glucose tolerance tests. RESEARCH DESIGN AND METHODS: 124 midlife Japanese (65 women, 66% with normal glucose tolerance) received dual-energy X-ray absorptiometry and 75 g oral glucose tolerance tests with multiple postload glucose and insulin measurements. Subjects were divided based on the relationship between postload and fasting glucose. Obesity measures, insulin resistance, insulin secretion, serum orosomucoid and adiponectin were cross-sectionally analyzed by analysis of variance and then Bonferroni's multiple comparison procedure. RESULTS: In 10 subjects (group A) and 19 subjects (group B), postload glucose fell below fasting glucose at 1 h and 2 h, respectively. In the remaining 95 subjects (group C), postload glucose never fell below fasting glucose. The insulinogenic index was lower and area under the glucose curve was higher in groups B and C as compared to group A (both p<0.05), whereas the Matsuda index, the homeostasis model assessment of insulin resistance, adipose insulin resistance (the product of fasting free fatty acid and insulin) and area under the insulin curve did not differ. Although there was no difference in fat mass index, trunk/leg fat ratio and adiponectin, orosomucoid was higher in group C as compared to group A (p<0.05). CONCLUSIONS: Lower early-phase insulin secretion and low-grade inflammation were associated with slower glucose disposal during an oral glucose tolerance test in midlife Japanese. The rate of glucose disposal was not related to adiposity and insulin resistance.

Reduced Birth Weight, Decreased Early-Phase Insulin Secretion, and Increased Glucose Concentrations after Oral Glucose Tolerance Test in Japanese Women Aged 20 Years with Family History of Type 2 Diabetes.

INTRODUCTION: We tested the hypothesis that family history of type 2 diabetes (FHD) is associated with reduced birth weight and reduced insulin secretion later in life. MATERIALS AND METHODS: Birth weight, body composition by whole-body dual-energy X-ray absorptiometry, and homeostasis model assessment-insulin resistance were compared between Japanese women aged 20 years with positive (n = 73) and negative (n = 258) FHD. A subsample of 153 women (57 with positive FHD) underwent a 75 g oral glucose tolerance test. Multivariate logistic regression analyses were used to identify the most important determinants of FHD. RESULTS: Women with positive as compared with negative FHD had lower birth weight (3132 ± 364 vs. 3238 ± 418 g, p = 0.04). However, the current fat mass index and trunk/leg fat ratio, sophisticated measures of general and abdominal fat accumulation, respectively, did not differ. Women with positive FHD had a lower insulinogenic index (2.4 ± 7.3 vs. 6.2 ± 16, p = 0.007) and higher area under the glucose curve (217 ± 47 vs. 198 ± 36 mg/dL/2 h, p = 0.006). However, fasting and postload insulinemia, homeostasis model assessment-insulin resistance, and Matsuda index did not differ. In multivariate logistic regression analysis, birth weight was marginally associated with FHD (odds ratio, 0.999; 95% confidential interval, 0.98-1.00000; p = 0.0509). CONCLUSIONS: FHD was associated not only with reduced birth weight but also with decreased early-phase insulin secretion and increased postload glucose concentrations in Japanese women aged 20 years. These findings may be in keeping with the fetal insulin hypothesis and provide some evidence that FHD can alter size at birth, probably through genetic and shared environmental components, which consequently resulted in decreased early-phase insulin secretion and increased glucose excursion in the early twenties. FHD was not related to sophisticated measures of general and abdominal adiposity and insulin resistance/sensitivity.

Higher circulating orosomucoid, an acute-phase protein, and reduced glucose-induced insulin secretion in middle-aged Japanese people with prediabetes.

INTRODUCTION: Circulating orosomucoid, an acute-phase protein, predicted type 2 diabetes mellitus risk in several Western countries. Here, we assessed serum orosomucoid (ORM) in relation to prediabetes in the Japanese. RESEARCH DESIGN AND METHODS: Participants consisted of 83 middle-aged Japanese subjects with normal glucose tolerance (NGT), 37 with prediabetes and 4 with newly identified diabetes, whose homeostasis model assessment-insulin resistance (HOMA-IR) averaged 1.1±0.7, 1.4±0.9 and 1.7±0.8, respectively. Body composition, serum inflammatory markers, adiponectin, ß-cell function and insulin resistance inferred from serum insulin kinetics during an oral glucose tolerance test were compared cross-sectionally between those with prediabetes and NGT. RESULTS: Serum orosomucoid, but not high-sensitivity C reactive protein, was elevated in prediabetes (190±29 vs 141±31 mg/dL) with further elevation in diabetes (295±52 mg/dL) (all p<0.001). Prediabetes was associated with lower Oral Disposition Index (the product of the Insulinogenic Index and Matsuda Index) with further depression in diabetes. No association was found with skeletal muscle mass, HOMA-IR, serum triglyceride, high-density lipoprotein (HDL) cholesterol and adiponectin. CONCLUSIONS: Higher circulating ORM and reduced glucose induced insulin secretion were found in middle-aged Japanese people with prediabetes in the absence of insulin resistance.

Determinants and correlates of adipose tissue insulin resistance index in Japanese women without diabetes and obesity.

INTRODUCTION: Determinants and correlates of a novel index of adipose tissue insulin resistance (AT-IR) (the product of fasting insulin and free fatty acid concentrations) were investigated in Japanese women without diabetes and obesity. RESEARCH DESIGN AND METHODS: Cross-sectional associations of AT-IR with fat mass and distribution, and IR-related cardiometabolic variables were examined in 210 young and 148 middle-aged women whose average body mass index (BMI) was <23 kg/m2 and waist was <80 cm. Multivariate linear regression analyses were used to identify most important determinants of AT-IR. RESULTS: Young and middle-aged women did not differ in AT-IR (3.5±2.7 and 3.2±2.1, respectively). In both young and middle-aged women, AT-IR was positively associated with trunk/leg fat ratio, a sophisticated measure of abdominal fat accumulation, fasting plasma glucose (FPG), fasting triglycerides (FTG), serum alanine aminotransferase and γ-glutamyl-transpeptidase (all p<0.05). Furthermore, in middle-aged but not in young women, AT-IR showed positive associations with BMI, waist, fat mass index, low-density lipoprotein cholesterol, apolipoprotein B and systolic and diastolic blood pressure (BP) (all p<0.05). AT-IR showed no association with hemoglobin A1c, high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 in two groups of women. On multivariate analysis including waist, FPG, FTG, HDL cholesterol and systolic BP as independent variables, FPG, FTG and HDL cholesterol emerged as independent determinants of AT-IR in young women (cumulative R2=0.141) and waist in middle-aged women (cumulative R2=0.056). In a model which included trunk/leg fat ratio instead of waist, trunk/leg fat ratio and systolic BP were determinants of AT-IR in middle-aged women (cumulative R2=0.093). Results did not alter in young women. CONCLUSIONS: AT-IR may be a simple and useful surrogate index of adipose tissue insulin resistance even in populations without diabetes and obesity.

Higher circulating adiponectin and lower orosomucoid were associated with postload glucose ≤70 mg/dL, a possible inverse marker for dysglycemia, in young Japanese women.

Objective: To examine whether serum adiponectin and orosomucoid were associated with postload glucose ≤70 mg/dL during an oral glucose tolerance test (OGTT), termed as postload low glycemia, a possible inverse marker for dysglycemia. Research design and methods: 75 g OGTTs were performed with multiple postload glucose and insulin measurements over a 30-120 min period in 168 normal-weight Japanese women (18-24 years). Insulin resistance (IR) and ß-cell function inferred from serum insulin kinetics during OGTT, fat mass and distribution by dual-energy X-ray absorptiometry (DXA), serum adiponectin and inflammatory markers were compared cross-sectionally between 39 women with and 129 women without postload low glycemia. Results: Of 168 women, 161 had normal glucose tolerance. Women with as compared with those without postload low glycemia had lower fasting and postload glycemia despite similar fasting and postload insulinemia. They had higher insulinogenic index (p=0.03) and lower adipose IR (a product of fasting free fatty acid and insulin, p=0.01), although DXA-derived general and central adiposity, the Matsuda Index and homeostasis model assessment-IR did not differ. In addition, they had higher adiponectin and lower orosomucoid (both p<0.001). Multivariate logistic regression analyses revealed that adiponectin (OR: 1.14, 95% CI 1.03 to 1.26, p=0.009) and orosomucoid (0.96, 0.93 to 0.97, p=0.008) were associated with postload low glycemia independently of adipose IR and insulinogenic index. Conclusions: Higher adiponectin and lower orosomucoid were associated with 70 or lower mg/dL of postload glucose, a possible inverse marker for dysglycemia, in young women independently of DXA-derived fat mass and distribution, insulin secretion and IR.

Association of Age and Anemia With Adiponectin Serum Levels in Normal-Weight Japanese Women.

BACKGROUND: Adiponectin serum levels are affected by sex, ethnicities, adiposity, age and several pathological conditions such as anemia. The prevalence of hyperadiponectinemia (≥ 20 mg/L) in relation to anemia (hemoglobin < 12 g/dL) was examined in normal-weight Japanese women. METHODS: Serum adiponectin and blood hemoglobin were measured in 311 young women aged 18 - 24 years (A), 148 of their middle-aged mothers aged 39 - 60 years (B) and 322 community-dwelling women aged ≥ 65 years (C) with a mean body mass index (BMI) of 20.4, 22.0 and 22.4 kg/m2, respectively. Elderly women were subdivided into three age groups: between 65 and 74 years (n = 95, X), between 75 and 84 years (n = 176, Y) and older than 85 years (n = 51, Z). RESULTS: The prevalence of hyperadiponectinemia (A: 3.9%, B: 3.4%, C: 22.7%, P < 0.001) was low and serum adiponectin (A: 11.5 ± 4.3 mg/L, B: 11.8 ± 4.9 mg/L, C: 15.3 ± 7.8 mg/L, P < 0.001) did not change until middle-aged but increased thereafter in a stepwise fashion (X: 18.9%, Y: 22.7%, Z: 35.3%, P = 0.07 and X: 13.9 ± 6.9 mg/L, Y: 15.1 ± 7.7 mg/L, Z: 18.7 ± 8.6 mg/L, P = 0.001, respectively). There were inverse associations of adiponectin with age (r = -0.201, P < 0.001) and hemoglobin (r = -0.318, P < 0.001) in elderly women but not even in young and middle-aged women combined. Furthermore, anemia was associated with higher prevalence of hyperadiponectinemia (34.8% vs. 20.6%, P = 0.01) and higher serum adiponectin (18.3 ± 9.4 mg/L vs. 14.5 ± 7.1 mg/L, P < 0.001) in elderly women but not in younger and middle-aged women. CONCLUSIONS: In normal-weight Japanese women, the prevalence of hyperadiponectinemia and serum adiponectin were increased and associated with anemia at 65 years of age and older.

Urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine levels in patients with type 2 diabetes.

Obesity modifies the association between sodium and potassium intake and blood pressure. However, the impact of obesity on the relationship between the sodium-potassium balance and cardiovascular risk in type 2 diabetes (T2DM) patients remains unclear. We investigated the relationship between the 24-h urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine (ADMA) level, which is a cardiovascular risk factor, in Japanese T2D patients with or without obesity. This cross-sectional study included 243 patients with T2DM who were hospitalized for diabetes education. Urinary sodium-to-potassium ratios were calculated from 24-h urine collection. The subjects were divided into two groups according to their BMIs (<25 and ≥25). The serum ADMA levels positively correlated with the urinary sodium-to-potassium ratios in non-obese patients, but not in obese patients. Multivariate linear regression analyses showed that the serum ADMA levels positively correlated with the urinary sodium-to-potassium ratios after adjustment for other confounders in non-obese patients. This correlation was observed in non-obese patients with hypertension, but not in those without hypertension. Measurement of the pulse wave velocity and intima-media thickness revealed that elevation of the serum ADMA levels was significantly associated with an increase in the degree of atherosclerotic progression in subjects with T2DM. Additionally, an assessment of dietary intake showed that the consumption of dairy products as well as of green and yellow vegetables was negatively associated with urinary sodium-to-potassium ratios in patients with T2DM. In conclusion, elevation of serum ADMA may be positively associated with the urinary sodium-to-potassium ratio in Japanese non-obese patients with T2DM.